Alternative Methotrexate Oral Formulation: Enhanced Aqueous Solubility, Bioavailability, Photostability, and Permeability
DC Field | Value | Language |
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dc.contributor.author | Giri, Bhupendra Raj | - |
dc.contributor.author | Yang, Hyun Seok | - |
dc.contributor.author | Song, Im-Sook | - |
dc.contributor.author | Choi, Han-Gon | - |
dc.contributor.author | Cho, Jung Hyun | - |
dc.contributor.author | Kim, Dong Wuk | - |
dc.date.accessioned | 2023-02-21T05:37:02Z | - |
dc.date.available | 2023-02-21T05:37:02Z | - |
dc.date.issued | 2022-10 | - |
dc.identifier.issn | 1999-4923 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/erica/handle/2021.sw.erica/111496 | - |
dc.description.abstract | The poor aqueous solubility and/or permeability and thereby limited bioavailability largely restricts the pharmaco-therapeutic implications of potent anticancer drugs such as methotrexate (MTX). Furthermore, MTX's inherently unstable nature makes it difficult to develop a viable oral formulation. In this study we developed the spray-dried amorphous inclusion complexes of MTX with native beta-cyclodextrin (beta-CD) and its derivatives, namely HP-beta-CD, M-beta-CD, and DM-beta-CD to enhance the aqueous solubility, photostability, permeability, and oral bioavailability of MTX in rats. Our findings show that the 1:1 stoichiometry ratio of MTX and CDs improves the aqueous solubility, stability, and pharmacokinetic profiles of the drug, the better results being obtained particularly with DM-beta-CD as a host, which has a higher complexation ability with the drug compared to other beta-CDs. Specifically, the pharmacokinetic analysis demonstrated 2.20- and 3.29-fold increments in AUC and Cmax, respectively, in comparison to free MTX. Even though the absorptive permeability of MTX and MTX/DM-beta-CD inclusion complexes was similar, the efflux of the absorbed MTX from ICs was significantly lower compared to the free MTX (4.6- vs. 8.0-fold). Furthermore, the physicochemical characterization employing SEM, DSC, and PXRD confirmed the transformation of crystalline MTX to its amorphous state. In solution, H-1 NMR studies revealed that MTX embedded into the DM-beta-CD cavity resulting in both H-3 and H-5 chemical shifts implied the presence of intermolecular interaction between the drug and CD moiety. It was, therefore, evident that an MTX IC could be a successful oral formulation technique, preventing MTX degradation and enhancing its pharmacologically relevant properties. | - |
dc.format.extent | 21 | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | Multidisciplinary Digital Publishing Institute (MDPI) | - |
dc.title | Alternative Methotrexate Oral Formulation: Enhanced Aqueous Solubility, Bioavailability, Photostability, and Permeability | - |
dc.type | Article | - |
dc.publisher.location | 스위스 | - |
dc.identifier.doi | 10.3390/pharmaceutics14102073 | - |
dc.identifier.scopusid | 2-s2.0-85140990776 | - |
dc.identifier.wosid | 000873542200001 | - |
dc.identifier.bibliographicCitation | Pharmaceutics, v.14, no.10, pp 1 - 21 | - |
dc.citation.title | Pharmaceutics | - |
dc.citation.volume | 14 | - |
dc.citation.number | 10 | - |
dc.citation.startPage | 1 | - |
dc.citation.endPage | 21 | - |
dc.type.docType | Article | - |
dc.description.isOpenAccess | Y | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Pharmacology & Pharmacy | - |
dc.relation.journalWebOfScienceCategory | Pharmacology & Pharmacy | - |
dc.subject.keywordPlus | BETA-CYCLODEXTRIN | - |
dc.subject.keywordPlus | INCLUSION COMPLEX | - |
dc.subject.keywordPlus | DELIVERY | - |
dc.subject.keywordPlus | RELEASE | - |
dc.subject.keywordAuthor | inclusion complex | - |
dc.subject.keywordAuthor | methotrexate | - |
dc.subject.keywordAuthor | solubility | - |
dc.subject.keywordAuthor | bioavailability | - |
dc.subject.keywordAuthor | permeability | - |
dc.subject.keywordAuthor | beta-cyclodextrin (beta-CD) | - |
dc.identifier.url | https://www.mdpi.com/1999-4923/14/10/2073 | - |
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